Browsing by Person "Randel, Olga"

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Untersuchungen zur Biogenese von Proteinen in der mitochondrialen Innenmembran
(2008) Randel, Olga; Rassow, Joachim
Mitochondria and prokaryotes show many similarities and it is a well established notion that they have common ancestors. It is therefore reasonable to expect significant similarities also in the biogenesis of their proteins. This study followed this idea in investigations on the biogenesis of protein complexes in the mitochondrial inner membrane. The yeast Saccharomyces cerevisiae served as a model organism. (1) γ-subunit of ATP synthases is highly conserved both in mitochondria and in prokaryotes. Previous studies demonstrated that deletions at the N- or C-terminus of the subunit entail only mild reductions in the enzymatic activity, and the reason of the conserved structure was enigmatic. The experiments of this study show that N- and C-terminus of the γ-subunit are essential for an efficient assembly in the ATP synthase. A deletion of 9 residues at the N-terminus or 10 residues at the C-terminus reduced the ratio of the subunit that assembled within 10 min. at 25°C by about 50%. Deletions of more than 9 N- or more than 20 C-terminal residues reduced the share of the assembled subunit by more than 90%. Yeast strains that synthesized a shortened γ- subunit did not grow on glycerole. N- and C-terminus are probably more relevant for assembly of the ATP synthase than for the transmission of energy. It is proposed that this is the case both for mitochondria and for prokaryotes. (2) The metabolite carrier proteins of the mitochondrial inner membrane were probably newly developed during the evolution of the eukaryotic cells. A common sequence motif of all carrier proteins is the carrier signature, P x (D/E) x x (K/R). The data of this study show that the carrier signature substantially facilitates the biogenesis of the dicarboxylate carrier (DIC). In particular, the translocation of this protein across the mitochondrial outer membrane is significantly accelerated. (3) The mitochondrial inner membrane protein Oxa1 is a member of a protein family that includes the bacterial protein YidC. Both Oxa1 and YidC act as mediators of protein insertion in their membranes, and both proteins participate in their own biogenesis. In this study, a series of experiments indicates that newly synthesized Oxa1 is not imported into the mitochondrial matrix, but accumulates in the inner membrane TIM23 translocase, for direct integration into the lipid bilayer. Oxa1 thereby shows a similar principle of membrane insertion as prokaryotic YidC. This was previously shown to first accumulate in the SecYEG translocase and then to directly integrate into the bacterial plasmamembrane. Oxa1 and YidC thus seem to resemble each other both in their structure and in their biogenesis. In summary, the experiments show that mitochondrial and prokaryotic proteins, after two billion years of separate evolution, have retained surprising similarities, even in molecular details of their function.